scholarly journals The Exercise-induced Improvement in Insulin-stimulated Glucose Uptake by Rat Skeletal Muscle Is Absent in Male AS160-Knockout Rats, Partially Restored by Muscle Expression of Phosphomutated AS160, and Fully Restored by Muscle Expression of Wildtype AS160

2021 ◽  
Author(s):  
Amy Zheng ◽  
Edward B. Arias ◽  
Haiyan Wang ◽  
Seong Eun Kwak ◽  
Xiufang Pan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Exercise Session ◽  
Rat Skeletal Muscle ◽  
Initial Experiment ◽  
Adeno Associated Virus ◽  
Glut4 Expression ◽  
Exercise Effect ◽  
Key Sites ◽  
Exercise Induced

One exercise session can elevate insulin-stimulated glucose uptake (ISGU) in skeletal muscle, but the mechanisms remain elusive. Circumstantial evidence suggests a role for Akt substrate of 160 kDa (AS160 or TBC1D4). We used genetic approaches to rigorously test this idea. The initial experiment evaluated AS160’s role for the postexercise increase in ISGU using muscles from male wildtype (WT) and AS160-knockout (AS160-KO) rats. The next experiment used AS160-KO rats with an adeno-associated virus (AAV) approach to determine if rescuing muscle AS160 deficiency could restore exercise’s ability to improve ISGU. The third experiment tested if eliminating the muscle GLUT4 deficit in AS160-KO rats via AAV-delivered GLUT4 would enable postexercise enhancement of ISGU. The final experiment employed AS160-KO rats and AAV-delivery of AS160 mutated to prevent phosphorylation of Ser588, Thr642, and Ser704 to evaluate their role in postexercise ISGU. We discovered: 1) AS160 expression was essential for postexercise increase in ISGU; 2) rescuing muscle AS160 expression of AS160-KO rats restored postexercise enhancement of ISGU; 3) restoring GLUT4 expression in AS160-KO muscle did not rescue the postexercise increase in ISGU; and 4) although AS160 phosphorylation on 3 key sites was not required for postexercise elevation in ISGU, it was essential for the full-exercise effect.

scholarly journals The Exercise-induced Improvement in Insulin-stimulated Glucose Uptake by Rat Skeletal Muscle Is Absent in Male AS160-Knockout Rats, Partially Restored by Muscle Expression of Phosphomutated AS160, and Fully Restored by Muscle Expression of Wildtype AS160

2021 ◽  
Author(s):  
Amy Zheng ◽  
Edward B. Arias ◽  
Haiyan Wang ◽  
Seong Eun Kwak ◽  
Xiufang Pan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Exercise Session ◽  
Rat Skeletal Muscle ◽  
Initial Experiment ◽  
Adeno Associated Virus ◽  
Glut4 Expression ◽  
Exercise Effect ◽  
Key Sites ◽  
Exercise Induced

One exercise session can elevate insulin-stimulated glucose uptake (ISGU) in skeletal muscle, but the mechanisms remain elusive. Circumstantial evidence suggests a role for Akt substrate of 160 kDa (AS160 or TBC1D4). We used genetic approaches to rigorously test this idea. The initial experiment evaluated AS160’s role for the postexercise increase in ISGU using muscles from male wildtype (WT) and AS160-knockout (AS160-KO) rats. The next experiment used AS160-KO rats with an adeno-associated virus (AAV) approach to determine if rescuing muscle AS160 deficiency could restore exercise’s ability to improve ISGU. The third experiment tested if eliminating the muscle GLUT4 deficit in AS160-KO rats via AAV-delivered GLUT4 would enable postexercise enhancement of ISGU. The final experiment employed AS160-KO rats and AAV-delivery of AS160 mutated to prevent phosphorylation of Ser588, Thr642, and Ser704 to evaluate their role in postexercise ISGU. We discovered: 1) AS160 expression was essential for postexercise increase in ISGU; 2) rescuing muscle AS160 expression of AS160-KO rats restored postexercise enhancement of ISGU; 3) restoring GLUT4 expression in AS160-KO muscle did not rescue the postexercise increase in ISGU; and 4) although AS160 phosphorylation on 3 key sites was not required for postexercise elevation in ISGU, it was essential for the full-exercise effect.

scholarly journals Postexercise improvement in glucose uptake occurs concomitant with greater γ3-AMPK activation and AS160 phosphorylation in rat skeletal muscle

2018 ◽  
Vol 315 (5) ◽  
pp. E859-E871 ◽  
Author(s):  
Haiyan Wang ◽  
Edward B. Arias ◽  
Mark W. Pataky ◽  
Laurie J. Goodyear ◽  
Gregory D. Cartee
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Ex Vivo ◽  
Contractile Activity ◽  
Exercise Session ◽  
Ampk Activation ◽  
Rat Skeletal Muscle ◽  
Ampk Activity ◽  
Exercise Induced

A single exercise session can increase insulin-stimulated glucose uptake (GU) by skeletal muscle, concomitant with greater Akt substrate of 160 kDa (AS160) phosphorylation on Akt-phosphosites (Thr642 and Ser588) that regulate insulin-stimulated GU. Recent research using mouse skeletal muscle suggested that ex vivo 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) or electrically stimulated contractile activity-inducing increased γ3-AMPK activity and AS160 phosphorylation on a consensus AMPK-motif (Ser704) resulted in greater AS160 Thr642 phosphorylation and GU by insulin-stimulated muscle. Our primary goal was to determine whether in vivo exercise that increases insulin-stimulated GU in rat skeletal muscle would also increase γ3-AMPK activity and AS160 site-selective phosphorylation (Ser588, Thr642, and Ser704) immediately postexercise (IPEX) and/or 3 h postexercise (3hPEX). Epitrochlearis muscles isolated from sedentary and exercised (2-h swim exercise; studied IPEX and 3hPEX) rats were incubated with 2-deoxyglucose to determine GU (without insulin at IPEX; without or with insulin at 3hPEX). Muscles were also assessed for γ1-AMPK activity, γ3-AMPK activity, phosphorylated AMPK (pAMPK), and phosphorylated AS160 (pAS160). IPEX versus sedentary had greater γ3-AMPK activity, pAS160 (Ser588, Thr642, Ser704), and GU with unaltered γ1-AMPK activity. 3hPEX versus sedentary had greater γ3-AMPK activity, pAS160 Ser704, and GU with or without insulin; greater pAS160 Thr642 only with insulin; and unaltered γ1-AMPK activity. These results using an in vivo exercise protocol that increased insulin-stimulated GU in rat skeletal muscle are consistent with the hypothesis that in vivo exercise-induced enhancement of γ3-AMPK activation and AS160 Ser704 IPEX and 3hPEX are important for greater pAS160 Thr642 and enhanced insulin-stimulated GU by skeletal muscle.

The effect of age on glucose uptake and GLUT1 and GLUT4 expression in rat skeletal muscle

2011 ◽  
Vol 30 (3) ◽  
pp. 191-197 ◽  
Author(s):  
J. M. Santos ◽  
S. A. Benite-Ribeiro ◽  
G. Queiroz ◽  
J. A. Duarte
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Rat Skeletal Muscle ◽  
Glut4 Expression ◽  
Effect Of Age

Effects of exercise training on skeletal muscle glucose uptake and transport

1993 ◽  
Vol 264 (3) ◽  
pp. C727-C733 ◽  
Author(s):  
G. J. Etgen ◽  
J. T. Brozinick ◽  
H. Y. Kang ◽  
J. L. Ivy
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Glucose Uptake ◽  
Protein Content ◽  
Glucose Transport ◽  
Exercise Session ◽  
Rat Skeletal Muscle ◽  
Glut 4 ◽  
Skeletal Muscle Glucose Uptake ◽  
Uptake And Transport

Exercise training increases the concentration of GLUT-4 protein in skeletal muscle that is associated with an increase in maximal insulin-stimulated glucose transport. The purpose of this study was to determine whether exercise training results in a long-lasting increase in insulin-stimulated glucose transport in rat skeletal muscle. Glucose uptake and skeletal muscle 3-O-methyl-D-glucose (3-MG) transport were determined during hindlimb perfusion in the presence of a maximally stimulating concentration of insulin (10 mU/ml). Hindlimb glucose uptake was approximately 29% above sedentary (Sed) levels in rats examined within 24 h (24H) of their last exercise session. However, when rats were examined 48 h (48H) after their last exercise session, hindlimb glucose uptake was not different from Sed levels. Maximal 3-MG transport was enhanced, above Sed levels, in red (RG; 72% increase) and white (WG; 44% increase) gastrocnemius and plantaris (Plan; 67% increase) muscles, but not soleus (Sol), of 24H rats. GLUT-4 protein content was significantly elevated in those muscles that exhibited enhanced 3-MG transport in 24H rats. GLUT-4 protein content was also elevated in RG, WG, and Plan of 48H rats and was not different from 24H rats. Despite the elevated GLUT-4 protein content, 3-MG transport in 48H rats was only slightly, although statistically not significantly, higher than in Sed rats. These results provide evidence that exercise training does not result in a persistent increase in skeletal muscle glucose uptake or transport, despite an increase in GLUT-4 protein content.

scholarly journals Effects of a brief high-fat diet and acute exercise on the mTORC1 and IKK/NF-κB pathways in rat skeletal muscle

2015 ◽  
Vol 40 (3) ◽  
pp. 251-262 ◽  
Author(s):  
Carlos M. Castorena ◽  
Edward B. Arias ◽  
Naveen Sharma ◽  
Gregory D. Cartee
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
High Fat Diet ◽  
Acute Exercise ◽  
Exercise Session ◽  
High Fat ◽  
Insulin Resistant ◽  
Mtorc1 Pathway ◽  
Exercise Induced

One exercise session can improve subsequent insulin-stimulated glucose uptake by skeletal muscle in healthy and insulin-resistant individuals. Our first aim was to determine whether a brief (2 weeks) high-fat diet (HFD) that caused muscle insulin resistance would activate the mammalian target of rapamycin complex 1 (mTORC1) and/or inhibitor of κB kinase/nuclear factor κB (IKK/NF-κB) pathways, which are potentially linked to induction of insulin resistance. Our second aim was to determine whether acute exercise that improved insulin-stimulated glucose uptake by muscles would attenuate activation of these pathways. We compared HFD-fed rats with rats fed a low-fat diet (LFD). Some animals from each diet group were sedentary and others were studied 3 h postexercise, when insulin-stimulated glucose uptake was increased. The results did not provide evidence that brief HFD activated either the mTORC1 (including phosphorylation of mTORSer2448, TSC2Ser939, p70S6KThr412, and RPS6Ser235/236) or the IKK/NF-κB (including abundance of IκBα or phosphorylation of NF-κBSer536, IKKα/βSer177/181, and IκBSer32) pathway in insulin-resistant muscles. Exercise did not oppose the activation of either pathway, as evidenced by no attenuation of phosphorylation of key proteins in the IKK/NF-κB pathway (NF-κBSer536, IKKα/βSer177/181, and IκBSer32), unaltered IκBα abundance, and no attenuation of phosphorylation of key proteins in the mTORC1 pathway (mTORSer2448, TSC2Ser939, and RPS6Ser235/236). Instead, exercise induced greater phosphorylation of 2 proteins of the mTORC1 pathway (PRAS40Thr246 and p70S6KThr412) in insulin-stimulated muscles, regardless of diet. Insulin resistance induced by a brief HFD was not attributable to greater activation of the mTORC1 or the IKK/NF-κB pathway in muscle, and exercise-induced improvement in insulin sensitivity was not attributable to attenuated activation of these pathways in muscle.

scholarly journals Exercise effects on γ3-AMPK activity, phosphorylation of Akt2 and AS160, and insulin-stimulated glucose uptake in insulin-resistant rat skeletal muscle

2020 ◽  
Vol 128 (2) ◽  
pp. 410-421
Author(s):  
Mark W. Pataky ◽  
Edward B. Arias ◽  
Haiyan Wang ◽  
Xiaohua Zheng ◽  
Gregory D. Cartee
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Exercise Session ◽  
Protein Kinase Activity ◽  
Insulin Resistant ◽  
Low Fat Diet ◽  
Ampk Activity ◽  
Exercise Induced ◽  
Amp Activated Protein Kinase ◽  
First Time

One exercise session can increase subsequent insulin-stimulated glucose uptake (ISGU) by skeletal muscle. Prior research on healthy muscle suggests that enhanced postexercise ISGU depends on elevated γ3-AMPK activity leading to greater phosphorylation of Akt substrate of 160 kDa (pAS160) on an AMPK-phosphomotif (Ser704). Phosphorylation of AS160Ser704, in turn, may favor greater insulin-stimulated pAS160 on an Akt-phosphomotif (Thr642) that regulates ISGU. Accordingly, we tested if exercise-induced increases in γ3-AMPK activity and pAS160 on key regulatory sites accompany improved ISGU at 3 h postexercise (3hPEX) in insulin-resistant muscle. Rats fed a high-fat diet (HFD; 2-wk) that induces insulin resistance either performed acute swim-exercise (2 h) or were sedentary (SED). SED rats fed a low-fat diet (LFD; 2 wk) served as healthy controls. Isolated epitrochlearis muscles from 3hPEX and SED rats were analyzed for ISGU, pAS160, pAkt2 (Akt-isoform that phosphorylates pAS160Thr642), and γ1-AMPK and γ3-AMPK activity. ISGU was lower in HFD-SED muscles versus LFD-SED, but this decrement was eliminated in the HFD-3hPEX group. γ3-AMPK activity, but not γ1-AMPK activity, was elevated in HFD-3hPEX muscles versus both SED controls. Furthermore, insulin-stimulated pAS160Thr642, pAS160Ser704, and pAkt2Ser474 in HFD-3hPEX muscles were elevated above HFD-SED and equal to values in LFD-SED muscles, but insulin-independent pAS160Ser704 was unaltered at 3hPEX. These results demonstrated, for the first time in an insulin-resistant model, that the postexercise increase in ISGU was accompanied by sustained enhancement of γ3-AMPK activation and greater pAkt2Ser474. Our working hypothesis is that these changes along with enhanced insulin-stimulated pAS160 increase ISGU of insulin-resistant muscles to values equaling insulin-sensitive sedentary controls. NEW & NOTEWORTHY Earlier research focusing on signaling events linked to increased insulin sensitivity in muscle has rarely evaluated insulin resistant muscle after exercise. We assessed insulin resistant muscle after an exercise protocol that improved insulin-stimulated glucose uptake. Prior exercise also amplified several signaling steps expected to favor enhanced insulin-stimulated glucose uptake: increased γ3-AMP-activated protein kinase activity, greater insulin-stimulated Akt2 phosphorylation on Ser474, and elevated insulin-stimulated Akt substrate of 160 kDa phosphorylation on Ser588, Thr642, and Ser704.

Impaired plasma FFA oxidation imposed by extreme CHO deficiency in contracting rat skeletal muscle

1994 ◽  
Vol 77 (2) ◽  
pp. 517-525 ◽  
Author(s):  
L. P. Turcotte ◽  
P. J. Hespel ◽  
T. E. Graham ◽  
E. A. Richter
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Glucose Uptake ◽  
Swimming Exercise ◽  
Rat Skeletal Muscle ◽  
Palmitate Oxidation ◽  
Plasma Ffa ◽  
Ffa Metabolism ◽  
Palmitate Uptake

The extent to which carbohydrate (CHO) availability affects free fatty acid (FFA) metabolism in contracting skeletal muscle is not well characterized. To study this question, rats were depleted of glycogen by swimming exercise and lard feeding 24 h before perfusion of their isolated hindquarters. After 20 min of preperfusion with a medium containing no glucose, palmitate (600 or 2,000 microM), and [1–14C]palmitate, flow was restricted to one hindlimb, which was electrically stimulated for 2 min to further deplete muscles of glycogen. After 2 min of recovery, glucose was added to the perfusate at final concentrations of 0, 6, or 20 mM, and after another 3 min muscles were stimulated for 30 min. At 6 and 2,000 microM palmitate, glucose uptake after 30 min of stimulation averaged 23.5 +/- 9.3 and 45.9 +/- 10.6 mumol.g-1.h-1 with 6 and 20 mM glucose, respectively. At 6 and 2,000 microM palmitate, palmitate uptake was lower (30–37%, P < 0.05) with 0 than with 6 or 20 mM glucose. At 600 microM palmitate, percent palmitate oxidation was higher (27%, P < 0.05) with 0 than with 6 or 20 mM glucose, resulting in similar total palmitate oxidation with the three glucose concentrations (0.28 +/- 0.01 mumol.g-1.h-1). At 2,000 microM palmitate, percent palmitate oxidation was not significantly different among glucose concentrations, resulting in a significantly lower rate of palmitate oxidation with 0 (0.62 +/- 0.18 mumol.g-1.h-1) than with 6 or 20 mM glucose (0.77 +/- 0.25 and 0.78 +/- 0.20 mumol.g-1.h-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Proteomic Investigation of Changes in Rat Skeletal Muscle after Exercise-Induced Fatigue

2012 ◽  
Vol 45 (1) ◽  
pp. 75-80 ◽  
Author(s):  
Liping Zhao ◽  
Wenhui Yan ◽  
Heng Xiang ◽  
Xiaoyang Wang ◽  
Haixuan Qiao
Keyword(s):  
Skeletal Muscle ◽  
Rat Skeletal Muscle ◽  
Proteomic Investigation ◽  
Exercise Induced
Sign in / Sign up

Export Citation Format

Share Document